The high contrast for breast pathology afforded by electromagnetic (EM) properties in the 300-3000 MHz[unreadable] range more than motivates the development of imaging technologies that seek to exploit these differences[unreadable] with normal tissue. Indeed, tomographic methods are attractive in this context because they generate spatial[unreadable] maps of imaged parameters in order to localize disease. Project III, Microwave Imaging and Spectroscopy[unreadable] (MIS), targets the development and evaluation of broadband, multi-spectral microwave tomography for[unreadable] breast imaging applications. During the current funding period, Project III has successfully deployed a[unreadable] clinical imaging system which transceives propagating EM fields through a non-contacting antenna array[unreadable] under computer-controlled axial translation to deliver comfortable exams to the pendant breast immersed in[unreadable] a fluid used to promote signal coupling into the region of interest. This system has been involved in more[unreadable] than 100 clinical sessions which have (i) determined that EM breast properties are higher and more[unreadable] heterogeneous than expected, (ii) begun to establish the normal breast response showing statistically[unreadable] significant increases in property values with increasing breast radiodensity, and (iii) suggested that there is[unreadable] sufficient property contrast to detect screening abnormalities. These encouraging developments and early[unreadable] clinical results motivate a new set of technical and clinical goals for the next funding period that center on[unreadable] three primary areas of investigation: (a) to develop and evaluate 3D microwave imaging, (b) to understand[unreadable] the impact of breast tissue composition on the images produced and (c) to validate resultant images through[unreadable] clinical studies organized by the Clinical Core. More specifically, the Project III aims for the proposed[unreadable] funding period are (1) to develop 3D imaging through faster, more accurate data acquisition and concomitant[unreadable] software advances to exploit anatomical priors through coregistration, high frequencies and multi-spectral[unreadable] methods, (2) to develop, validate and utilize a probe-based measurement system for local property studies at[unreadable] the time of surgery but prior to histopathology on breast tissues previously imaged in vivo, (3) to validate the[unreadable] new system advances in phantoms and clinical cases correlated with MR (Magnetic Resonance) and (4) to[unreadable] continue clinical studies in.collaboration with the Clinical Core which target screening abnormalities[unreadable] recommended for biopsy, palpable masses on clinical breast exams and locally-advanced cancers receiving[unreadable] neoadjuvant therapy. If successful, it is expected that these aims will generate sufficient evidence to allow[unreadable] convincing estimates of the potential of MIS as an alternative for differential diagnosis, and pilot data in[unreadable] support of a role in treatment prognosis and therapy monitoring which would inform decisions on initiation of[unreadable] multi-center trials with MIS technology in the future.